Stratification of heart failure patients for cardiac recovery upon cardiac unloading by left ventricular assist device therapy: addressing the molecular, epigenetic, and proteomic changes associated with reverse cardiac remodelling.
In this project FRRB finances Partner number 2: IRCCS Istituto Clinico Humanitas, Milano. The Principal Investigator esponsible of the project is Dr. Marie Luise Bang.
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Pathology of interest: |
Heart failure |
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Area of research: |
Cardiology |
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Start date: |
July 2019 |
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End date: |
June 2022 |
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Funding: |
€ 500.000,00 |
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Project partners: |
University Medical Center Freiburg – leading partner IRCCS Istituto Clinico Humanitas; Humanitas Mirasole Spa Bordeaux University |
PROJECT SUMMARY
Limited regenerative capacity of the human heart leads to remodelling, and eventually heart failure (HF). At present, heart transplantation or left ventricular assist device (LVAD) implantation are the only available treatment options. LVADs are currently used as a bridge to transplant or destination therapy; however, in a subset of patients, LVADs may serve as a bridge to recovery (BTR), where cardiac unloading and recovery of heart function enable LVAD explantation.
Unfortunately, LVAD explantation is not a common practice at most cardiac centers, and during post LVAD follow up, dedicated protocols for promoting cardiac remodelling and monitoring of cardiac function are often lacking.
Based on genome wide epigenetic, transcriptomic, and proteomic analyses in LVAD patients and a mouse model of cardiac unloading, we aim to provide insights into the mechanisms associated with unloaded mediated reverse cardiac remodelling (RCR). Moreover, we aim to identify biomarkers to predict cardiac recovery, which, together with clinical characteristics, could facilitate the identification of patients that may be candidates for BTR, allowing for appropriate post LVAD monitoring of cardiac function, myocardial conditioning, and pharmacological therapy to improve outcomes and increase the likelihood of recovery and successful LVAD explantation.
In addition, we will optimize a novel contact free, non invasive imaging technique based on live video cardiograms of cardiac contraction during open chest cardiac surgery for monitoring of cardiac function during LVAD implantation surgery, expected to lead to better medical decision making during surgery, improving post operative care, and cardiac outcomes.
Furthermore, we will study the effect of modulation of a number of long non coding RNAs that are dysregulated in HF and normalized after unloading, to determine whether they may represent targets for therapies, which alone or in conjunction with LVAD support can promote RCR.